The functional roles of poly(ethylene glycol)‐lipid and lysolipid in the drug retention and release from lysolipid‐containing thermosensitive liposomes in vitro and in vivo

Banno, Brian; Ickenstein, Ludger M.; Chiu, Gigi Ngar Chee; Bally, Marcel B.; Thewalt, Jenifer; Brief, Elana; Wasan, Ellen K.

doi:10.1002/jps.21988

Cited by 105 publications

(80 citation statements)

References 49 publications

(49 reference statements)

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“…[31][32][33][34] The ability of LTSL to release encapsulated drug was found to be superior to that of conventional DPPC-based thermosensitive liposomes from which the encapsulated drug is released relatively slowly. [33][34][35][36][37][38] Inclusion of ~10 mol% of the lysolipid, such as mono-stearoylsn-glycero-3-phosphatidylcholine (MSPC), produced significantly higher membrane permeability, with the highest permeability occurring at phase transition temperature which increased the encapsulated drug release. 36 The encapsulated drug could fast release from the thermosensitive liposomes during hyperthermia treatment in the vasculature of tumor tissues site.…”

Section: Introductionmentioning

confidence: 99%

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

Wang¹,

Wang²,

Zhong³

et al. 2015

IJN

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Clotted plasma proteins are present on the walls of tumor vessels and in tumor stroma. Tumor-homing peptide Cys-Arg-Glu-Lys-Ala (CREKA) could recognize the clotted plasma proteins in tumor vessels. Thermosensitive liposomes could immediately release the encapsulated drug in the vasculature of the heated tumor. In this study, we designed a novel form of targeted thermosensitive liposomes, CREKA-modified lysolipid-containing thermosensitive liposomes (LTSLs), containing doxorubicin (DOX) (DOX-LTSL-CREKA), to investigate the hypothesis that DOX-LTSL-CREKA might target the clotted plasma proteins in tumor vessels as well as tumor stroma and then exhibit burst release of the encapsulated DOX at the heated tumor site. We also hypothesized that the high local drug concentration produced by these thermosensitive liposomes after local hyperthermia treatment will be useful for treatment of multidrug resistance. The multidrug-resistant human breast adenocarcinoma (MCF-7/ADR) cell line was chosen as a tumor cell model, and the targeting and immediate release characteristics of DOX-LTSL-CREKA were investigated in vitro and in vivo. Furthermore, the antitumor activity of DOX-LTSL-CREKA was evaluated in MCF-7/ADR tumor-bearing nude mice in vivo. The targeting effect of the CREKA-modified thermosensitive liposomes on the clotted plasma proteins was confirmed in our in vivo imaging and immunohistochemistry experiments. The burst release of this delivery system was observed in our in vitro temperature-triggered DOX release and flow cytometry analysis and also by confocal microscopy experiments. The antitumor activity of the DOX-LTSL-CREKA was confirmed in tumor-bearing nude mice in vivo. Our findings suggest that the combination of targeting the clotted plasma proteins in the tumor vessel wall as well as tumor stroma by using CREKA peptide and temperature-triggered drug release from liposomes by using thermosensitive liposomes offers an attractive strategy for chemotherapeutic drug delivery to tumors.

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Section: Introductionmentioning

confidence: 99%

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

Wang¹,

Wang²,

Zhong³

et al. 2015

IJN

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“…79 Banno et al demonstrated that the presence of MSPC, rather than PEG 2000-DSPE, in DPPC liposomes would give rise to the rapid drug-release profile in vitro, suggesting that lysolipid is the more important component in determining the rate of TSL content release. 80 Indeed, Banno's in vivo data showed that the presence of 9.6 mol% MSPC in TSL could result in more rapid elimination of the encapsulated doxorubicin (T 1/2 = 1.29 h), compared with the formulation without lysolipid (T 1/2 = 2.91 h). In 2007, Dromi et al compared the accumulation of doxorubicin in mice tumors among free doxorubicin, Doxil, and ThermoDox.…”

Section: Clinical Studies Of Liposomal-based Anticancer Drugs: Doxorumentioning

confidence: 99%

Clinical development of liposome based drugs: formulation, characterization, and therapeutic efficacy

Chang

Yeh²

2011

IJN

336

159

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Abstract:Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposomebased drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized.

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“…HE treatment of solid tumors with thermosensitive liposomes (TSL) has emerged as a viable clinical alternative to traditional chemotherapy, increasing the anti-tumor efficacy of existing chemotherapeutics, and concomitantly reducing side effects [1][2][3][4][5][6][7]. Drug-loaded TSL are administered intravenously to the bloodstream, and as the liposomes circulate within a locally heated tissue, a phase transition in the lipid membrane results in a burst-release of drug.…”

Section: Introductionmentioning

confidence: 99%

“…The most clinically advanced TSL is ThermoDox (Celsion, Phase II and III), composed of DPPC, lyso-PC, and DSPE-PEG 2000 ( 86:10:4, molar ratio): this three-part liposome encapsulates doxorubicin (DOX), a potent anticancer therapeutic [1][2][3][4][5][6][7], and is proceeding well through clinical trials for liver cancer and recurrent breast cancer of the chest wall (www.celsion.com). ThermoDOX treatment is currently coupled with radiofrequency (RF) ablation for liver, or focused microwave for breast cancer of the chest wall.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound drug targeting to tumors with thermosensitive liposomes

Ernsting

Worthington

May

et al. 2011

2011 IEEE International Ultrasonics Symposium

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Induction of local tissue hyperthermia is emerging as a valuable tool in cancer therapy, as temperatures between 39-43 o C are sufficient to trigger release of drug from thermosensitive liposomes (TSL), but is not harmful to normal tissue. Despite significant advances in spatial and dynamic control of ultrasound, temperature profiles in heated tissues are never homogenous, and an ideal TSL should achieve complete local release over the entire hyperthermia range. We have developed a TSL exhibiting a sensitive temperature release profile (39-43 o C) with excellent stability at 37 o C. We prepared a TSL composed of DPPC lipid and Brij78 surfactant, and loaded this hyperthermia-activated-cytotoxic (HaT) TSL with doxorubicin (DOX). EMT-6 breast tumors located on a Balb/c mouse footpad were instantaneously heated to 42-43 o C using a 3.9 MHz planar transducer: body temperature did not elevate above 37 o C, and complete remission of the EMT-6 breast cancer tumors was observed.Mice treated with standard DOX chemotherapy (at same 10 mg/kg dose as HaT) did not exhibit any tumor inhibition effects compared to control mice. By histological examination, no physiological damage to normal tissues was induced by ultrasound heating, and mice treated with HaT DOX regained normal tissue appearance and function posttreatment.This study confirms the benefit of coupling ultrasound induced hyperthermia with a sensitive TSL formulation.

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The functional roles of poly(ethylene glycol)‐lipid and lysolipid in the drug retention and release from lysolipid‐containing thermosensitive liposomes in vitro and in vivo

Cited by 105 publications

References 49 publications

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

Clinical development of liposome based drugs: formulation, characterization, and therapeutic efficacy

Ultrasound drug targeting to tumors with thermosensitive liposomes

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